Presentations will focus on a wide range of
disease areas including multiple myeloma, lymphoma, acute myeloid
leukemia, myelodysplastic syndromes and beta-thalassemia and novel
technologies such as CAR-T cell therapy
Celgene Corporation (NASDAQ:CELG) today announced that data from
282 abstracts, including more than 60 oral presentations,
evaluating Celgene investigational agents and investigational uses
of marketed products will be presented at the 59th American Society
of Hematology Annual Meeting between Dec. 9-12 in Atlanta, GA.
Presentations will include investigational data from Celgene
agents in company-sponsored or investigator-initiated studies.
“Disease altering advances in hematology are coming at a more
rapid pace than ever and we are looking forward to new insights
into the treatment of deadly blood cancers and other serious
diseases,” said Nadim Ahmed, President, Hematology and Oncology for
Celgene. “Presentations highlighting data from more than 150
studies in multiple myeloma utilizing the foundation of IMiD®
therapies in investigational uses continue to grow the body of
evidence for these treatments. We are also excited about results
from novel technologies such as CAR-T cell therapy and other
pipeline candidates across multiple disease areas that demonstrate
our commitment to patients with life-threatening hematologic
diseases.”
Selected abstracts include*:
Multiple Myeloma
Data will be presented from the immunotherapy-focused
collaboration between Celgene and bluebird bio demonstrating
significant potential in multiple myeloma research:
Abstract #740; Oral; Monday, Dec. 11. 3 p.m., Hall C1, Durable
clinical responses in heavily pretreated patients with
relapsed/refractory multiple myeloma: Updated results from a
multicenter study of bb2121 anti-BCMA CAR T cell therapy
(Kochenderfer)
Among the more than 150 studies including IMiD-based regimens,
including investigational combinations, there are presentations
across the myeloma continuum. Some of these include:
Abstract #1811; Poster; Saturday, Dec. 9, 5:30 p.m., Hall A2,
Safety and Efficacy of Pomalidomide (POM) + Low-Dose Dexamethasone
(LoDEX) + Daratumumab (DARA) As Second- or Third-Line Therapy in
Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)
after Lenalidomide (LEN)-Based Treatment (Tx) Failure (Siegel)
Abstract #400; Oral; Sunday, Dec. 10, 10:15 a.m., C101,
Response-Adapted Lenalidomide Maintenance in Newly Diagnosed,
Transplant-Eligible Multiple Myeloma: Results from the Multicenter
Phase III GMMG-MM5 Trial (Goldschmidt)
Abstract #402; Oral; Sunday, Dec. 10, 10:45 a.m., C101, Curative
Strategy for High-Risk Smoldering Myeloma (GEM-CESAR): Carfilzomib,
Lenalidomide and Dexamethasone (KRd) As Induction Followed By
HDT-ASCT, Consolidation with Krd and Maintenance with Rd
(Mateos)
Abstract #436; Oral; Sunday, Dec. 10, 12:45 p.m., Hall C4,
Lenalidomide maintenance significantly improves outcomes compared
to observation irrespective of cytogenetic risk: Results of the
Myeloma XI trial (Jackson)
Abstract #739; Oral; Monday, Dec. 11, 2:45 p.m., Hall C1,
Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus
Lenalidomide and Dexamethasone (Rd) in Relapsed or Refractory
Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of
Pollux (Dimopoulos)
Abstract #743; Oral; Monday, Dec. 11, 3:45 p.m., Hall C1,
Overall Survival (OS) of Patients with Relapsed/Refractory Multiple
Myeloma (RRMM) Treated with Carfilzomib, Lenalidomide, and
Dexamethasone (KRd) Versus Lenalidomide and Dexamethasone (Rd):
Final Analysis from the Randomized Phase 3 Aspire Trial
(Stewart)
Abstract #837; Oral; Monday, Dec. 11 5 p.m., Hall C1, A
Multicenter Open Label Phase II Study of Pomalidomide,
Cyclophosphamide and Dexamethasone in Relapse Multiple Myeloma
Patients Initially Treated with Lenalidomide, Bortezomib and
Dexamethasone (Garderet)
Abstract #904; Oral; Monday, Dec. 11, 7 p.m., Hall C4, Minimal
Residual Disease in the Maintenance Setting in Myeloma: Prognostic
Significance and Impact of Lenalidomide (de Tute)
Abstract #905; Oral; Monday, Dec. 11, 7:15 p.m., Hall C4, Impact
of Next-Generation Flow (NGF) Minimal Residual Disease (MRD)
Monitoring in Multiple Myeloma (MM): Results from the
Pethema/GEM2012 Trial (Paiva)
Lymphomas/Chronic Lymphocytic Leukemia
(CLL)
Updated data from the CAR-T program JCAR-017 in partnership with
Juno Therapeutics will be presented in multiple studies:
Abstract #193; Oral; Saturday, Dec. 9, 2 p.m., C101, Auditorium
Patient Characteristics and Pre-Infusion Biomarkers of Inflammation
Correlate with Clinical Outcomes after Treatment with the Defined
Composition, CD19-Targeted CAR T Cell Product, JCAR017
(Siddiqi)
Abstract #194; Oral; Saturday, Dec. 9, 2:15 p.m., C101,
Auditorium Predicting Clinical Response and Safety of JCAR017 in
B-NHL Patients: Potential Importance of Tumor Microenvironment
Biomarkers and CAR T-Cell Tumor Infiltration (Swanson)
Abstract #581; Oral; Monday, Dec. 11, 8 a.m., A411-A412, High
Durable CR Rates in Relapsed/Refractory (R/R) Aggressive B-NHL
Treated with JCAR017 (TRANSCEND NHL 001): Defined Composition
CD19-Directed CAR T Cell Product Allows for Dose Finding and
Definition of Pivotal Cohort (Abramson)
Several studies presented focus on investigational
chemotherapy-free treatment approaches in indolent lymphoma and
CLL, including R2 (REVLIMID® + rituximab), while further data from
Celgene’s pipeline demonstrates our commitment to new lymphoma
research.
Abstract #154; Oral; Saturday, Dec. 9, 12:45 p.m., A411-A412,
Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell
Lymphoma: 5-year Follow-up and Correlative Analysis from a
Multi-center Phase II Study (Ruan)
Abstract #192; Oral; Saturday, Dec. 9, 3:15 p.m., A411-A412, A
Phase I, Open–Label, Multicenter Trial of Oral Azacitidine (CC-486)
Plus R–CHOP in Patients with High-Risk, Previously Untreated
Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or
Transformed Lymphoma (Martin)
Abstract #411; Oral; Sunday, Dec. 10, 12:30 p.m., Hall C1,
CC-122, a Novel Cereblon Modulating Agent, in Combination with
Obinutuzumab (GA101) in Patients with Relapsed and Refractory (R/R)
B–cell Non–Hodgkin Lymphoma (NHL) (Michot)
Abstract #482; Oral; Sunday, Dec. 10, 4:45 p.m., Hall C1, A
3-Arm Randomized Phase II Trial with Bendamustine/Rituximab Therapy
in Untreated High Risk (HR) Follicular Lymphoma (FL): Bortezomib
Induction or Novel IMiD Continuation (BIONIC) Study from the
ECOG-ACRIN Cancer Research Group (Evens)
Abstract #729; Oral; Monday, Dec. 11, 3:15 p.m., C101
Auditorium, Lenalidomide Treatment Restores In Vivo T Cell Activity
in Relapsed/Refractory FL and DLBCL (Menard)
Myeloid Diseases
In acute myeloid leukemia (AML), new data for investigational
uses of IDHIFA® (enasidenib) in patients in the relapsed/refractory
and front-line settings in combinations, as well as new phase II
data for CC486 in post-transplant maintenance for AML and in
patients with MDS will be presented.
Abstract #1299; Poster; Saturday, Dec. 9, 5:30 p.m., Hall A2,
Continuing Enasidenib Treatment for Patients with Mutant-IDH2
(mIDH2) Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
with Stable Disease May Result in Improved Survival and Responses
over Time (Stein)
Abstract #638; Oral; Monday, Dec. 11, 10:45 a.m., Murphy
Ballroom 1-2, Enasidenib Monotherapy Is Effective and
Well-tolerated in Patients with Previously Untreated Mutant-IDH2
(mIDH2) Acute Myeloid Leukemia (AML) (Pollyea)
Abstract #639; Oral; Monday, Dec. 11, 11 a.m., Murphy Ballroom
1-2, Mutant Isocitrate Dehydrogenase (mIDH) Inhibitors, Enasidenib
or Ivosidenib, in Combination with Azacitidine (AZA): Preliminary
Results of a Phase 1b/2 Study in Patients with mIDH Newly Diagnosed
Acute Myeloid Leukemia (AML) (DiNardo)
Abstract #726; Oral; Monday, Dec. 11, 4 p.m., Murphy Ballroom
1-2, A phase 1 trial of ivosidenib and enasidenib combined with
standard induction chemotherapy in newly diagnosed AML patients
with an IDH1 and/or IDH2 mutation (Stein)
Abstract #751; Oral; Monday, Dec. 11, 2:45 p.m., C211-C213,
Quality of Life in Patients with β-Thalassemia: Transfusion
Dependent Versus Non-Transfusion Dependent (Cappellini)
Abstract #4512; Poster; Monday, Dec. 11, 6 p.m., Hall A2, Final
Analysis of the Phase I/II Study of CC-486 (Oral Azacitidine)
Maintenance Therapy after Allogeneic Stem Cell Transplantation
(Allo-SCT) in Patients with Acute Myeloid Leukemia (AML) or
Myelodysplastic Syndromes (MDS) (de Lima)
The safety and efficacy of investigational agents and/or
investigational uses of approved marketed products have not been
established. There is no guarantee that the agents will receive
health authority approval or become commercially available in any
country for the uses being investigated.
A complete listing of abstracts can be found on the ASH Web site
at http://www.hematology.org/Annual-Meeting/Abstracts/
*All times Eastern Standard Time
About REVLIMID®REVLIMID®
(lenalidomide) in combination with dexamethasone (dex) is
indicated for the treatment of patients with multiple myeloma
(MM)REVLIMID is indicated as maintenance therapy in patients
with MM following autologous hematopoietic stem cell
transplantation (auto-HSCT)REVLIMID® is
indicated for the treatment of patients with transfusion-dependent
anemia due to low-or intermediate-1–risk myelodysplastic syndromes
(MDS) associated with a deletion 5q cytogenetic abnormality with or
without additional cytogenetic
abnormalitiesREVLIMID® is indicated for the
treatment of patients with mantle cell lymphoma (MCL) whose disease
has relapsed or progressed after two prior therapies, one of which
included bortezomibREVLIMID is not indicated and is not
recommended for the treatment of patients with chronic lymphocytic
leukemia (CLL) outside of controlled clinical trials
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and
VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
Do not use REVLIMID during pregnancy. Lenalidomide, a
thalidomide analogue, caused limb abnormalities in a developmental
monkey study. Thalidomide is a known human teratogen that causes
severe life-threatening human birth defects. If lenalidomide is
used during pregnancy, it may cause birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative
pregnancy tests before starting REVLIMID treatment. Females of
reproductive potential must use 2 forms of contraception or
continuously abstain from heterosexual sex during and for 4 weeks
after REVLIMID treatment. To avoid embryo-fetal exposure to
lenalidomide, REVLIMID is only available through a restricted
distribution program, the REVLIMID REMS®
program).
Information about the REVLIMID REMS® program is
available at www.celgeneriskmanagement.com or by calling the
manufacturer’s toll-free number 1-888-423-5436.
Hematologic Toxicity (Neutropenia and
Thrombocytopenia)
REVLIMID can cause significant neutropenia and
thrombocytopenia. Eighty percent of patients with del 5q MDS had to
have a dose delay/reduction during the major study. Thirty-four
percent of patients had to have a second dose delay/reduction.
Grade 3 or 4 hematologic toxicity was seen in 80% of patients
enrolled in the study. Patients on therapy for del 5q MDS should
have their complete blood counts monitored weekly for the first 8
weeks of therapy and at least monthly thereafter. Patients may
require dose interruption and/or reduction. Patients may require
use of blood product support and/or growth factors.
Venous and Arterial
Thromboembolism
REVLIMID has demonstrated a significantly increased risk of
deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as
risk of myocardial infarction and stroke in patients with MM who
were treated with REVLIMID and dexamethasone therapy. Monitor for
and advise patients about signs and symptoms of thromboembolism.
Advise patients to seek immediate medical care if they develop
symptoms such as shortness of breath, chest pain, or arm or leg
swelling. Thromboprophylaxis is recommended and the choice of
regimen should be based on an assessment of the patient’s
underlying risks.
CONTRAINDICATIONS
Pregnancy: REVLIMID can cause fetal harm when
administered to a pregnant female and is contraindicated in females
who are pregnant. If this drug is used during pregnancy or if the
patient becomes pregnant while taking this drug, the patient should
be apprised of the potential risk to the fetus
Allergic Reactions: REVLIMID is contraindicated in
patients who have demonstrated hypersensitivity (e.g., angioedema,
Stevens-Johnson syndrome, toxic epidermal necrolysis) to
lenalidomide
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity: See Boxed WARNINGS
- Females of
Reproductive Potential: See Boxed WARNINGS
- Males:
Lenalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even
if they have undergone a successful vasectomy. Male patients taking
REVLIMID must not donate sperm
- Blood
Donation: Patients must not donate blood during treatment
with REVLIMID and for 4 weeks following discontinuation of the drug
because the blood might be given to a pregnant female patient whose
fetus must not be exposed to REVLIMID
REVLIMID REMS® Program: See Boxed WARNINGS:
Prescribers and pharmacies must be certified with the REVLIMID REMS
program by enrolling and complying with the REMS requirements;
pharmacies must only dispense to patients who are authorized to
receive REVLIMID. Patients must sign a Patient-Physician Agreement
Form and comply with REMS requirements; female patients of
reproductive potential who are not pregnant must comply with the
pregnancy testing and contraception requirements and males must
comply with contraception requirements
Hematologic Toxicity: REVLIMID can cause significant
neutropenia and thrombocytopenia. Monitor patients with neutropenia
for signs of infection. Advise patients to observe for bleeding or
bruising, especially with use of concomitant medications that may
increase risk of bleeding. MM: Patients taking REVLIMID/dex or
REVLIMID maintenance therapy should have their complete blood
counts (CBC) assessed every 7 days for the first 2 cycles, on days
1 and 15 of cycle 3, and every 28 days thereafter. MDS: Patients on therapy for del 5q
MDS should have their complete blood counts monitored weekly for
the first 8 weeks of therapy and at least monthly thereafter.
Patients may require dose interruption and/or dose reduction.
Please see the Black Box WARNINGS for further information.
MCL: Patients taking
REVLIMID for MCL should have their CBCs monitored weekly for the
first cycle (28 days), every 2 weeks during cycles 2-4, and then
monthly thereafter. Patients may require dose interruption and/or
dose reduction
Venous and Arterial Thromboembolism: See Boxed WARNINGS:
Venous thromboembolic events (DVT and PE) and arterial thromboses
(MI and CVA) are increased in patients treated with REVLIMID.
Patients with known risk factors, including prior thrombosis, may
be at greater risk and actions should be taken to try to minimize
all modifiable factors (e.g., hyperlipidemia, hypertension,
smoking). Thromboprophylaxis is recommended and the regimen should
be based on patient’s underlying risks. ESAs and estrogens may
further increase the risk of thrombosis and their use should be
based on a benefit-risk decision
Increased Mortality in Patients with CLL: In a clinical
trial in the first-line treatment of patients with CLL, single
agent REVLIMID therapy increased the risk of death as compared to
single agent chlorambucil. Serious adverse cardiovascular
reactions, including atrial fibrillation, myocardial infarction,
and cardiac failure, occurred more frequently in the REVLIMID arm.
REVLIMID is not indicated and not recommended for use in CLL
outside of controlled clinical trials
Second Primary Malignancies (SPM): In clinical trials in
patients with MM receiving REVLIMID, an increase of hematologic
plus solid tumor SPM, notably AML and MDS, have been observed.
Monitor patients for the development of SPM. Take into account both
the potential benefit of REVLIMID and risk of SPM when considering
treatment
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with REVLIMID/dex. Pre-existing
viral liver disease, elevated baseline liver enzymes, and
concomitant medications may be risk factors. Monitor liver enzymes
periodically. Stop REVLIMID upon elevation of liver enzymes. After
return to baseline values, treatment at a lower dose may be
considered
Allergic Reactions: Angioedema and serious dermatologic
reactions including Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) have been reported. These events can be
fatal. Patients with a prior history of Grade 4 rash associated
with thalidomide treatment should not receive REVLIMID. REVLIMID
interruption or discontinuation should be considered for Grade 2-3
skin rash. REVLIMID must be discontinued for angioedema, Grade 4
rash, exfoliative or bullous rash, or if SJS or TEN is suspected
and should not be resumed following discontinuation for these
reactions. REVLIMID capsules contain lactose; risk-benefit of
treatment should be evaluated in patients with lactose
intolerance
Tumor Lysis Syndrome (TLS): Fatal instances of TLS have
been reported during treatment with lenalidomide. The patients at
risk of TLS are those with high tumor burden prior to treatment.
These patients should be monitored closely and appropriate
precautions taken
Tumor Flare Reaction (TFR): TFR has occurred during
investigational use of lenalidomide for CLL and lymphoma.
Monitoring and evaluation for TFR is recommended in patients with
MCL. Tumor flare may mimic the progression of disease (PD). In
patients with Grade 3 or 4 TFR, it is recommended to withhold
treatment with REVLIMID until TFR resolves to ≤ Grade 1. REVLIMID
may be continued in patients with Grade 1 and 2 TFR without
interruption or modification, at the physician’s discretion
Impaired Stem Cell Mobilization: A decrease in the number
of CD34+ cells collected after treatment (>4 cycles) with
REVLIMID has been reported. Consider early referral to transplant
center to optimize timing of the stem cell collection
Thyroid Disorders: Both hypothyroidism and
hyperthyroidism have been reported. Measure thyroid function before
start of REVLIMID treatment and during therapy
ADVERSE REACTIONS
Multiple Myeloma
- In newly diagnosed: The most
frequently reported Grade 3 or 4 reactions included neutropenia,
anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain,
hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT,
hyperglycemia, and leukopenia. The highest frequency of infections
occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%).
There were more Grade 3 and 4 and serious adverse reactions of
infection in Arm Rd Continuous than either Arm MPT or Rd18
- The most common adverse reactions
reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%),
neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%),
insomnia (28%), rash (26%), decreased appetite (23%), cough (23%),
dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms
(20%), and thrombocytopenia (20%)
- Maintenance Therapy Post
Auto-HSCT: The most frequently reported Grade 3 or 4 reactions
in ≥20% (REVLIMID arm) included neutropenia, thrombocytopenia, and
leukopenia. The serious adverse reactions of lung infection and
neutropenia (more than 4.5%) occurred in the REVLIMID arm
- The most frequently reported adverse
reactions in ≥20% (REVLIMID arm) across both maintenance studies
(Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia
(72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper
respiratory tract infection (27%, 11%), bronchitis (5%, 47%),
nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%,
23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%),
asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%,
21%)
- After at least one prior
therapy: The most common adverse reactions reported in ≥20%
(REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neutropenia
(42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%),
muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs
23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain
(26% vs 19%), upper respiratory tract infection (25% vs 16%),
dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22%
vs 11%), rash (21% vs 9%), tremor (21% vs 7%), and weight decreased
(20% vs 15%)
Myelodysplastic
Syndromes
- Grade 3 and 4 adverse events reported
in ≥ 5% of patients with del 5q MDS were neutropenia (53%),
thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%),
leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain
(5%)
- Adverse events reported in ≥15% of del
5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia
(58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%),
constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia
(22%), pyrexia (21%), back pain (21%), peripheral edema (20%),
cough (20%), dizziness (20%), headache (20%), muscle cramp (18%),
dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%),
upper respiratory tract infection (15%)
Mantle Cell Lymphoma
- Grade 3 and 4 adverse events reported
in ≥5% of patients treated with REVLIMID in the MCL trial (N=134)
included neutropenia (43%), thrombocytopenia (28%), anemia (11%),
pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%),
dyspnea (6%), and febrile neutropenia (6%)
- Adverse events reported in ≥15% of
patients treated with REVLIMID in the MCL trial included
neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia
(31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%),
rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%),
constipation (16%), and leukopenia (15%)
DRUG INTERACTIONS
Periodic monitoring of digoxin plasma levels is recommended due
to increased Cmax and AUC with concomitant REVLIMID therapy.
Patients taking concomitant therapies such as erythropoietin
stimulating agents or estrogen containing therapies may have an
increased risk of thrombosis. It is not known whether there is an
interaction between dex and warfarin. Close monitoring of PT and
INR is recommended in patients with MM taking concomitant
warfarin
USE IN SPECIFIC POPULATIONS:
- PREGNANCY: See Boxed WARNINGS:
If pregnancy does occur during treatment, immediately discontinue
the drug and refer patient to an obstetrician/gynecologist
experienced in reproductive toxicity for further evaluation and
counseling. There is a REVLIMID pregnancy exposure registry that
monitors pregnancy outcomes in females exposed to REVLIMID during
pregnancy as well as female partners of male patients who are
exposed to REVLIMID. This registry is also used to understand the
root cause for the pregnancy. Report any suspected fetal exposure
to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088
and also to Celgene Corporation at 1-888-423-5436
- LACTATION: There is no
information regarding the presence of lenalidomide in human milk,
the effects of REVLIMID on the breastfed infant, or the effects of
REVLIMID on milk production. Because many drugs are excreted in
human milk and because of the potential for adverse reactions in
breastfed infants from REVLIMID, advise female patients not to
breastfeed during treatment with REVLIMID
- PEDIATRIC USE: Safety and
effectiveness have not been established in pediatric patients
- RENAL IMPAIRMENT: Adjust the
starting dose of REVLIMID based on the creatinine clearance value
and for patients on dialysis
Please see full Prescribing Information, including
Boxed WARNINGS.
About POMALYST/IMNOVID
Indication
POMALYST® (pomalidomide) is a thalidomide analogue indicated, in
combination with dexamethasone, for patients with multiple myeloma
who have received at least two prior therapies including
lenalidomide and a proteasome inhibitor and have demonstrated
disease progression on or within 60 days of completion of the last
therapy.
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL
THROMBOEMBOLISM
Embryo-Fetal Toxicity
- POMALYST is contraindicated in pregnancy. POMALYST is a
thalidomide analogue. Thalidomide is a known human teratogen that
causes severe birth defects or embryo-fetal death. In females of
reproductive potential, obtain 2 negative pregnancy tests before
starting POMALYST treatment.
- Females of reproductive potential must use 2 forms of
contraception or continuously abstain from heterosexual sex during
and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution
program called POMALYST REMS®.
Venous and Arterial Thromboembolism
- Deep venous thrombosis (DVT), pulmonary embolism (PE),
myocardial infarction, and stroke occur in patients with multiple
myeloma treated with POMALYST. Prophylactic antithrombotic measures
were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on
assessment of the patient’s underlying risk factors.
CONTRAINDICATIONS
- Pregnancy: POMALYST can cause fetal
harm and is contraindicated in females who are pregnant. If
POMALYST is used during pregnancy or if the patient becomes
pregnant while taking this drug, the patient should be apprised of
the potential risk to a fetus.
WARNINGS AND PRECAUTIONS
- Embryo-Fetal
Toxicity & Females of Reproductive Potential: See Boxed
WARNINGS
- Males:
Pomalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
POMALYST and for up to 4 weeks after discontinuing POMALYST, even
if they have undergone a successful vasectomy. Males must not
donate sperm.
- Blood
Donation: Patients must not donate blood during treatment
with POMALYST and for 1 month following discontinuation of POMALYST
therapy because the blood might be given to a pregnant female
patient whose fetus must not be exposed to POMALYST.
- POMALYST
REMS® Program: See Boxed WARNINGS
- Prescribers and pharmacies must be
certified with the POMALYST REMS program by enrolling and
complying with the REMS requirements; pharmacies must only dispense
to patients who are authorized to receive POMALYST. Patients must
sign a Patient-Physician Agreement Form and comply with REMS
requirements; female patients of reproductive potential who are not
pregnant must comply with the pregnancy testing and contraception
requirements and males must comply with contraception
requirements.
- Further information about the
POMALYST REMS program is available at
www.CelgeneRiskManagement.com or by telephone at
1-888-423-5436.
- Venous and
Arterial Thromboembolism: See Boxed WARNINGS. Patients
with known risk factors, including prior thrombosis, may be at
greater risk, and actions should be taken to try to minimize all
modifiable factors (e.g., hyperlipidemia, hypertension, smoking).
Thromboprophylaxis is recommended, and the choice of regimen should
be based on assessment of the patient’s underlying risk
factors.
- Hematologic
Toxicity: Neutropenia (46%) was the most
frequently reported Grade 3/4 adverse reaction in patients taking
POMALYST in clinical trials, followed by anemia and
thrombocytopenia. Monitor complete blood counts weekly for the
first 8 weeks and monthly thereafter. Patients may require dose
interruption and/or modification.
- Hepatotoxicity: Hepatic failure,
including fatal cases, has occurred in patients treated with
POMALYST. Elevated levels of alanine aminotransferase and bilirubin
have also been observed in patients treated with POMALYST. Monitor
liver function tests monthly. Stop POMALYST upon elevation of liver
enzymes. After return to baseline values, treatment at a lower dose
may be considered.
- Hypersensitivity Reactions:
Angioedema and severe dermatologic reactions have been reported.
Discontinue POMALYST for angioedema, skin exfoliation, bullae, or
any other severe dermatologic reactions, and do not resume
therapy.
- Dizziness and
Confusional State: In patients taking POMALYST in
clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7%
a confusional state (3% Grade 3 or 4). Instruct patients to avoid
situations where dizziness or confusional state may be a problem
and not to take other medications that may cause dizziness or
confusional state without adequate medical advice.
- Neuropathy: In patients taking
POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3
in one trial) and 12% peripheral neuropathy.
- Second Primary
Malignancies: Cases of acute myelogenous leukemia
have been reported in patients receiving POMALYST as an
investigational therapy outside of multiple myeloma.
- Tumor Lysis
Syndrome (TLS): TLS may occur in patients treated
with POMALYST. Patients at risk are those with high tumor burden
prior to treatment. These patients should be monitored closely and
appropriate precautions taken.
ADVERSE REACTIONS
Nearly all patients treated with POMALYST + low-dose dex
experienced at least one adverse reaction (99%). The most common
adverse reactions included neutropenia (51.3%), fatigue and
asthenia (46.7%), upper respiratory tract infection (31%),
thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%),
diarrhea (22%), constipation (21.7%), back pain (19.7%), cough
(20%), pneumonia (19.3%), bone pain (18%), edema peripheral
(17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and
nausea (15%). Grade 3 or 4 adverse reactions included neutropenia
(48.3%), thrombocytopenia (22%), and pneumonia (15.7%).
DRUG INTERACTIONS
Avoid concomitant use of POMALYST with strong inhibitors of
CYP1A2. Consider alternative treatments. If a strong CYP1A2
inhibitor must be used, reduce POMALYST dose by 50%.
USE IN SPECIFIC POPULATIONS
- Pregnancy: See
Boxed WARNINGS. If pregnancy does occur during
treatment, immediately discontinue the drug and refer patient to an
obstetrician/gynecologist experienced in reproductive toxicity for
further evaluation and counseling. There is a POMALYST pregnancy
exposure registry that monitors pregnancy outcomes in females
exposed to POMALYST during pregnancy as well as female partners of
male patients who are exposed to POMALYST. This registry is also
used to understand the root cause for the pregnancy. Report any
suspected fetal exposure to POMALYST to the FDA via the MedWatch
program at 1-800-FDA-1088 and also to Celgene Corporation at
1-888-423-5436.
- Lactation: There is no information
regarding the presence of pomalidomide in human milk, the effects
of POMALYST on the breastfed infant, or the effects of POMALYST on
milk production. Pomalidomide was excreted in the milk of lactating
rats. Because many drugs are excreted in human milk and because of
the potential for adverse reactions in breastfed infants from
POMALYST, advise a nursing woman to discontinue breastfeeding
during treatment with POMALYST.
- Pediatric
Use: Safety and effectiveness have not been
established in pediatric patients.
- Geriatric
Use: No dosage adjustment is required for
POMALYST based on age. Patients >65 years of age were more
likely than patients ≤65 years of age to experience pneumonia.
- Renal
Impairment: Reduce POMALYST dose by 25% in
patients with severe renal impairment requiring dialysis. Take dose
of POMALYST following hemodialysis on hemodialysis days.
- Hepatic
Impairment: Reduce POMALYST dose by 25% in
patients with mild to moderate hepatic impairment and 50% in
patients with severe hepatic impairment.
- Smoking
Tobacco: Advise patients that smoking may reduce
the efficacy of POMALYST. Cigarette smoking reduces the AUC of
pomalidomide by 32% by CYP1A2 induction.
Please see full Prescribing Information,
including Boxed WARNINGS.
About IDHIFA
IDHIFA (enasidenib) is indicated for the treatment of adult
patients with relapsed or refractory acute myeloid leukemia with an
isocitrate dehydrogenase-2 mutation as detected by an FDA-approved
test.
Important Safety Information
WARNING: DIFFERENTIATION SYNDROME
Patients treated with IDHIFA have experienced symptoms of
differentiation syndrome, which can be fatal if not treated.
Symptoms may include fever, dyspnea, acute respiratory distress,
pulmonary infiltrates, pleural or pericardial effusions, rapid
weight gain or peripheral edema, lymphadenopathy, bone pain, and
hepatic, renal, or multi-organ dysfunction. If differentiation
syndrome is suspected, initiate corticosteroid therapy and
hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed WARNING. In the
clinical trial, 14% of patients treated with IDHIFA experienced
differentiation syndrome. Differentiation syndrome has been
observed with and without concomitant hyperleukocytosis, as early
as 10 days and at up to 5 months after IDHIFA initiation. If
differentiation syndrome is suspected, initiate systemic
corticosteroids and hemodynamic monitoring until improvement. Taper
corticosteroids only after resolution of symptoms. Differentiation
syndrome symptoms may recur with premature discontinuation of
corticosteroids. If severe pulmonary symptoms requiring intubation
or ventilator support and/or renal dysfunction persist for more
than 48 hours after initiation of corticosteroids, interrupt IDHIFA
until signs and symptoms are no longer severe. Hospitalization for
close observation and monitoring of patients with pulmonary and/or
renal manifestation is recommended.
Embryo-Fetal Toxicity: Based on animal embryo-fetal
toxicity studies, IDHIFA can cause embryo-fetal harm when
administered to a pregnant woman. Advise females of reproductive
potential and males with female partners of reproductive potential
to use effective contraception during treatment with IDHIFA and for
at least 1 month after the last dose. Pregnant women, patients
becoming pregnant while receiving IDHIFA, or male patients with
pregnant female partners should be apprised of the potential risk
to the fetus.
ADVERSE REACTIONS
- The most common adverse reactions
(≥20%) included total bilirubin increased (81%), calcium decreased
(74%), nausea (50%), diarrhea (43%), potassium decreased (41%),
vomiting (34%), decreased appetite (34%), and phosphorus decreased
(27%)
- The most frequently reported ≥Grade 3
adverse reactions (≥5%) included total bilirubin increased (15%),
potassium decreased (15%), phosphorus decreased (8%), calcium
decreased (8%), diarrhea (8%), differentiation syndrome (7%),
non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and
nausea (5%)
- Serious adverse reactions were reported
in 77.1% of patients. The most frequent serious adverse reactions
(≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting
(3%), decreased appetite (3%), tumor lysis syndrome (5%), and
differentiation syndrome (8%). Differentiation syndrome events
characterized as serious included pyrexia, renal failure acute,
hypoxia, respiratory failure, and multi-organ failure
LACTATION
Many drugs are excreted in human milk and because of the
potential for adverse reactions in breastfed infants, advise women
not to breastfeed during treatment with IDHIFA and for at least 1
month after the last dose.
Please see full Prescribing Information,
including Boxed WARNING
About Celgene
Celgene Corporation, headquartered in Summit, New
Jersey, is an integrated global biopharmaceutical company engaged
primarily in the discovery, development and commercialization of
innovative therapies for the treatment of cancer and inflammatory
diseases through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com. Follow
Celgene on Social
Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
Forward-Looking Statements
This press release contains forward-looking statements, which
are generally statements that are not historical facts.
Forward-looking statements can be identified by the words
"expects," "anticipates," "believes," "intends," "estimates,"
"plans," "will," “outlook” and similar expressions. Forward-looking
statements are based on management’s current plans, estimates,
assumptions and projections, and speak only as of the date they are
made. We undertake no obligation to update any forward-looking
statement in light of new information or future events, except as
otherwise required by law. Forward-looking statements involve
inherent risks and uncertainties, most of which are difficult to
predict and are generally beyond our control. Actual results or
outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual
Report on Form 10-K and our other reports filed with the Securities
and Exchange Commission.
Hyperlinks are provided as a convenience and for informational
purposes only. Celgene bears responsibility for the security or
content of external websites or websites outside of its
control.
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